Cardiovascular Systems 14 - Coronary heart disease

Question 1

List the risk factors for coronary heart disease

Answer 1

• Modifiable factors (smoking, lipids, blood pressure, diabetes)
• Non-modifiable factors (age, sex and genetic background)
• There is MULTIPLICATION of risk with different factors

Question 2

List the changes in epidemiology over the last decade, relating to coronary heart disease.

Answer 2

• Reduced hyperlipidaemia
• Reduced hypertension
• Increased obesity and diabetes
• Changing pathology due to altered risk factors

Question 3

List the interventions for atherosclerosis

Answer 3

• There is a window of opportunity for primary prevention, such as life style changes and risk factor management
• Once complicated, clinical intervention is needed (secondary prevention, catheter based interventions, treatment of heart failure)

Question 4

List the cell types involved in atherosclerosis

Answer 4

• Vascular endothelial cells
• Monocyte-macrophages
• Vascular smooth muscle cells
• Platelets
• T lymphocytes

Question 5

Describe the role of vascular endothelial cells in atherosclerosis

Answer 5

• Barrier function

- Leukocyte recruitment

Question 6

Describe the role of monocyte-macrophages in atherosclerosis

Answer 6

• Foam cell formation
• Cytokine and growth factor release
• Source of free radicals
• Metalloproteinases

Question 7

Describe the role of vascular smooth muscle cells in atherosclerosis

Answer 7

• Migration and proliferation
• Collagen synthesis
• Remodelling and fibrous cap formation

Question 8

Describe the role of platelets in atherosclerosis

Answer 8

• Thrombus generation

- Cytokine and growth factor release

Question 9

Describe the role of t lymphocytes in atherosclerosis

Answer 9

Macrophage activation

Question 10

How are macrophage subtypes regulated?

Answer 10

By combination of transcription factors binding to regulatory sequences on DNA.

Question 11

List the two main classes of macrophages

Answer 11

• Inflammatory macrophages are adapted to kill microorganisms
• Resident macrophages are homeostatic, suppressing inflammatory activity

Question 12

List the functions of resident macrophages

Answer 12

• Suppress inflammatory activity
• Alveolar resident macrophages are involved in surfactant lipid homeostasis
• Osteoclases
• In the spleen there is iron homeostasis

Question 13

Why are LDLs involved in atherosclerosis formation?

Answer 13

• They are oxidised and modified due to the action of free radicals on LDL, which occurs following binding to proteoglycans in the sub-endothelial layer
• They are highly inflammatory and toxic, found in the vessel wall

Question 14

Describe the structure of LDLs

Answer 14

• Docking molecule is like an address
• Lipid monolayer is only one molecule thick, similar to a cell membrane
• There is cargo fat for fuel

Question 15

What can be observed in familial hyperlipidemia?

Answer 15

• Elevated cholesterol, as there is failure to clear LDL
• xanthomas (patches on the skin due to deposition of lipids)
• High risk of early atherosclerosis

Question 16

What LDL receptors are present in atherosclerosis?

Answer 16

• Scavenger receptors, not under feedback control hoover up modified LDL
• Other LDL receptors are regulated by cholesterol

Question 17

What are the two macrophage scavenger receptors?

Answer 17

• Receptor A is CD204, binds to oxidised LDL, dead cells and gram +ve bacteria
• Receptor B CD36, binds to oxidised LDL, malaria and dead cells

Question 18

What enzymes are present in macrophages to modify LDL?

Answer 18

• NADPH oxidase

- Myeloperoxidase

Question 19

What inflammatory factors are expressed by plaque macrophages?

Answer 19

• Cytokines are protein immune hormones that activate endothelial cell adhesion molecules (VCAM 1)
• Chemokines are small proteins chemoattractant to monocytes (MCP1)

Question 20

What growth factors are produced by macrophages in the VSMC?

Answer 20

• Platelet derived growth factor (chemotaxis, mitosis, cell survival)
• Transforming growth factor beta (increased collagen synthesis and matrix deposition)

Question 21

What is the function of metalloproteinases?

Answer 21

• Enzymes that activate each other by proteolysis
• Degrade collagen
• Catalytic mechanism is based on zinc
• Plaque erosion or rupture

Question 22

List the characteristics of vulnerable plaques.

Answer 22

• Large eccentric lipid-rich necrotic core
• Increased apoptosis
• Reduced collagen
• Thin fibrous cap
• Infiltrate of activated macrophages

Question 23

Describe the process of macrophage apoptosis in atherosclerosis

Answer 23

• OxLDL derived metabolites are toxic
• Macrophage foam cells have systems to maintain survival following toxic lipid loagind, but once overwhelmed macrophages die via apoptosis
• Macrophage tissue factors and toxic lipids released into the central death zone (lipid necrotic core)
• Thrombogenic and toxic material accumulates until plaque wall rupture

Question 24

What activates Nuclear factor kappa B?

Answer 24

• Scavenger receptors
• Toll-like receptors
• Cytokine receptors

Question 25

What inflammatory genes were switched on by NFkB?

Answer 25

• Matrix metalloproteinases

- Inducible nitric oxide synthase